Decreased electromechanical activity of guinea pig circular muscle during pregnancy

GASTROENTEROLOGY

Decreased Electromechanical Muscle During Pregnancy HENRY

P. PARKMAN,*

MICHAEL

B. WANG,*

1993;105:1306-1312

Activity of Guinea Pig Circular

and JAMES

P. RYAN*

Departments of *Medicine and *Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania

BaclWound: Delayed gastric emptying has been reported during pregnancy; however, its underlyingmechanism is poorly understood. The purpose of this study was to determine if electromechanical activity of antral circular muscle is decreased during pregnancy. Methods: Antral muscle strips from third-trimester pregnant and age-matched control virgin female guinea pigs were studied in vitro. Results: Spontaneous and bethanechol-induced phasic antral contractions from pregnant guinea pigs were reduced significantly in force compared with control virgin animals. Although the resting membrane potentials were similar, the electric slow waves of pregnant animals displayed significant decreases in upstroke amplitude, plateau amplitude, and number of spikes during the plateau potential compared with control animals. The voltage-tension relationship was similar in pregnant and control animals. Conclusions: This study indicates that (1) the force of antral circular muscle contractions is decreased during pregnancy and (2) this decreased force is secondary to a diminished slow wave depolarization. The results suggest that a change in electromechanical activity of gastric muscle is a cause of altered gastric motility in pregnancy.

turns to normal by 4 days postpartum.

This observa-

tion suggests that the pregnancy-induced

gastroparesis

results from gastric motor dysfunction The mechanism

astrointestinal

gravidarum), effects

nausea and vomiting

gallbladder

These disturbances

during pregnancy in-

disturbances

clude heartburn,

stasis,

and

(emesis

constipation.’

may be mediated by the inhibitory

of progesterone

on gastrointestinal

smooth

muscle during pregnancy.2A The nausea and vomiting

that occur during preg-

nancy may be caused by decreased resting pressure within the lower esophageal sphincte2 and changes in gastric motility. 5 Although several studies have suggested that gastric emptying is delayed in pregnancy,G8 others have not confirmed these findings.“-‘* One possible explanation for this discrepancy is that most studies in pregnant women have measured gastric emptying of liquids rather than using the more sensitive solid-phase gastric emptying test. It also has been reported that delayed gastric emptying occurs during pregnancy in the guinea pig.13 The delayed emptying persists in the immediate postpartum period but re-

uterus.13

of this delayed gastric emptying

poorly understood

is

and is the subject of the present

study. To test the hypothesis that delayed gastric emptying during pregnancy chanical

is caused by changes in electrome-

activity of the gastric smooth muscle, studies

of guinea pig gastric antrum were performed to (1) determine whether contractility

in vitro

of gastric antral

circular muscle is decreased during pregnancy evaluate electromechanical

and (2)

coupling of antral smooth

muscle during pregnancy.

Materials and Methods Pregnant female guinea pigs at 50-55 days gestation (third trimester of normal 70-day pregnancy)13 and agematched virgin female guinea pigs were used. The third trimester of the guinea pig pregnancy was chosen because delayed gastric emptying has been shown in vivo during this gestational Guinea

G

and not second-

ary to effects of an enlarged intra-abdominal

period.13 pigs were fasted overnight

stomach

was removed

cervical

dislocation

kg

or with sodium

intraperitoneally).

opened contents

After

along the greater by washing

tion in mmol/L: 1.2; NaHCO,, muscle

strips

female

guinea

before

pentobarbital

removal,

curvature

solution

pigs were prepared

(composi11.5). The

and control

in a similar

was

of residual 2.5; MgCl,,

1.2; and glucose,

the pregnant

(50 mg/

stomach

120; KCl, 4.6; CaCl,,

22; NaHJ’O,, both

the

and cleansed

with Krebs’ buffer

NaCI,

from

the study. The

after the guinea pig had been killed by

virgin

manner.

The

mucosa was removed from the antrum. Full-thickness strips of midantrum (3 X 8 mm) were cut from either side of the greater

curvature

with the longer

axis parallel

muscle fibers. The strip was transferred ing chamber,

which

was continuously

warmed (35”C), preoxygenated Krebs’ solution at 5 mL/min.

to the circular

to an in vitro recordperfused

with

pre-

(95% 02, 5% CO,; pH 7.4) Temperature was monitored

by a thermistor probe (Yellow Springs Instrument Co. Inc., Yellow Springs, OH) submerged in the bathing solution. A 0 1993 by the American Gastroenterological 0016-5085/93/$3.00

Association

November

1993

segment

DECREASED

of each strip was carefully

(Dow

Corning

Corp.,

Midland,

with the serosal side down end of the strip ducer circular

Bioscience,

muscle

tension.

antral

muscle

ments

until

antral

contractions

Muscle phasic

the muscarinic

that

in the Results (lo-’

This suggests

bethanechol-induced

electrical

puller

(model

holder served

CA). The electrodes

(World

stage of a preamplifier

(model

773; World

2230; Tetronix

Inc., Beaverton,

220; Gould

microelectrode

through

the location

the preparation

of the impaled

differentiate

smooth

intracellular

drop on impalement

ing membrane izations

near

potential

and a maintained

with spontaneous

plateau amplitude, fast depolarizations Changes

quantitatively: of slow waves,

duration (spikes)

in muscle

tension

to

submucosal

border.‘4T’7 The crite-

impalement

(slow waves). 14*” The following

ters were analyzed potential, frequency

it of

cell in order the

were

a rapid

negative

electrical

rest-

depolar-

slow wave parameresting upstroke

membrane amplitude,

of slow waves, and number of during the plateau potential.” and intracellular

electrical

in

one strip was used, the values Un-

and

basal

phasic

and virgin guinea pigs. Two-way

(ANOVA) the pregnant

of

contractions

be-

analysis

was used to test for significance and virgin

guinea

of be-

pigs’ dose response

increase

in the amplitude

P val-

above basal contractions.” significant.

Effect of Pregnancy on Antral Contractility

of the preparation

muscle

and cells next to the myenteric

ria for a successful voltage

cells

of experiments

more than one cell in

Results

the

of the location

per

t test was used to test for significance

parameters

pregnant

variance

(model

with

for tis-

a single value for that animal.

were considered

“on side” to determine

smooth

muscle

Student’s wave

than

to obtain

contractions

In these studies,

the depth

cell. The thin cross section pinning

strip or more

Instru

derived

as kilograms

+ SEM

in which

effects of the bethanechol-induced

micro-

surface

optically

expressed

as mean

In animals

of the phasic

Precision

cross-sectional using

force was normalized

and

ues of <0.05

impaled

the submucosa.i6

to determine

are expressed

a muscle

OH).

randomly

area

animals.

OR) and to a chart recorder

cells were

Contractile

An Ag-Ag

to an oscilloscope

Inc., Cleveland,

muscle

the impaled

Data

tween

X

to be 1.056 g/cm3.3*18 The accu-

to the head

Instruments).

the microelectrode

was connected

3

Corp.,

area was calculated

centimeter.

tween

40 and 70 MR.

dry with

OHaus

Area = Mass/(Density

previously

different

slow

Instrument

held in a Plexiglas

Precision

which

prevented

measurements.3,” sue cross-sectional

paired

Precision

me-

strip length

blotted

GAllO;

for determining

verified

were averaged

muscle

were filled with

between

were firmly

to connect

was not possible

Sutter

relationship:

atropine

where the mass is in grams, the length in centimeters,

area has been

square

and

any neurally

the muscle

(model

and the den.@y is assumed

on

(1 0e6 mol/L),

was removed,

weighed

racy of this method

with a Brown-Flam-

P-77;

and

the

Tetrodotoxin

(10m6 mol/L),

strip

1307

decreasing

hydrochloride

Park, NJ). The cross-sectional

Length),

contractions.

(World

paper,

using the following

(1 Om6

from smooth

FL) pulled

KC1 and had a tip resistance

The microelectrodes

border

antral

recordings

Inc., Sarasota,

Smooth

atropine

while

osmolarity.

were used to inhibit

The

to

(Sigma

had no effect

using glass electrodes

Co., San Francisco,

(model

effects.

of

acts directly on smooth musreceptors, as shown in other gastrointestinal

ing microelectrode

ments),

diated

that bethanechol

Instruments

Cl wire

(lop6 mol/L)

Florham

Concentrations

whereas

concentration to maintain

At the end of each experiment,

studies showed

to lop6 mol/L)

IN PREGNANCY

propranolol

was measured.

are the final concen-

Preliminary

contractions,

cells were obtained

electrode

tension)

hydrochloride

section

the chamber.

abolished

cle muscarinic tissues.15 Intracellular

mol/L

and frequency

CONTRACTILITY

hydrochloride

sulfate

filter

of tonic

bethanechol

( 1O-’ mol/L),

increphasic

(L,A.14

(amplitude

concentration

phentolamine

the

in small

Co., St. Louis, MO) were studied.

tetrodotoxin

mol/L)

equilibration,

stretched

and development

bethanechol-induced

trans-

force of the spontaneous

responses

perfusing

force

the potassium

sodium

MA) to measure

90-minute

was observed

agonist

of bethanechol trations

Natick,

was progressively

tension

Chemical

After

creasing

side up. The free

to an isometric

South

the maximum

contractions

to the Sylgard of the chamber

and submucosal

was attached

(Harvard

pinned

MI) floor

ANTRAL

ac-

tivity in response to changing the Krebs’ buffer solution (4.6 mmol/L potassium) to high potassium (20 mmol/L)-containing Krebs’ solution was also evaluated. The 20 mmol/L potassium-containing Krebs’ solution was prepared by in-

In vitro

midantrum

circular

smooth

displayed

muscle

tions. With each strip set at L,, maximum

amplitude

tions)

in the presence

L),

and

(length

to minimize

phasic

and

any neurally

fects, the force of spontaneous antral significantly (1” = 0.045) reduced guinea

pigs (0.78 ? 0.12 kg/cm2)

trol virgin

females

contrac-

to produce

the

contrac-

(1 O-’ mol/

of tetrodotoxin

mol/L),

pig

guinea

phasic

of spontaneous

(lop6

propranolol

(10e6 mol/L)

from

spontaneous

phentolamine mediated

ef-

contractions was in the pregnant

compared

(1.10 * 0.11 kg/cm2;

with conFigure

M).

The frequency of spontaneous antral contractions was similar in pregnant and virgin female guinea pigs (6.0 + 0.2 vs 6.1 f 0.2 contractions/min, respectively; P > 0.10). Bethanechol, a muscarinic cholinergic agonist, in various concentrations (0.1-10 pmol/L) increased the amplitude of phasic antral contractions, with no significant increase in baseline tone. In Figure lB, the effects of four different doses of bethanechol in increasing the

1308

PARKMAN ET AL.

1.5

GASTROENTEROLOGY Vol. 105, No. 5

pregnant

A

1

guinea

the decreased ijg 3 Y 5, ._ E P

1

1.0

0.5

0.0

Virain Fecale

-ii

contractility

during

pregnancy.

circular

smooth

displayed

of antral

muscle

from

electromechanical

guinea

from

potential,

tential.

pig antral

during

the plateau

of cells. Studies guinea brane

plateau

slow wave 1). Thus, 5

tions. Each muscle strip is set at the length to produce the maximum amplitude of spontaneous phasic contractions (L,,). Tetrodotoxin, propranolol, and phentolamine were present to minimize any neurally mediated effects. The results are expressed as force per cross-sectional area (tension). (A) The force of spontaneous basal phasic antral contractions in pregnant guinea pigs (n = 7) was significantly (P = 0.045) reduced compared with control virgin females (n = 7). *P < 0.05 by unpaired Student’s t test. (6) The dose-response effects of bethanechol(O.1, 1, 5, and 10 pmol/L) in increasing the amplitude of phasic contractions above the basal spontaneous contractions in muscle strips from pregnant (0; n = 7) and virgin (0; n = 7) guinea pigs. The active force of phasic contractions in response to bethanechol stimulation was significantly reduced in the pregnant guinea pigs compared with the virgin females (P = 0.023 by two-way ANOVA).

and

pregnant

guinea

pigs.

are compared The

increase

and 20 pregnant

female

resting

mem-

and slow wave

in the upstroke

and number female

po-

fast spikes

in the majority

are similar

am-

of spikes per

guinea

pigs (Table

force of spontaneous

Effect of Pregnancy Characteristics To determine

antral

con-

wave depolarization

on Voltage-Tension

whether during

the

pregnancy

for the decreased

force of spontaneous

tions,

generated

the forces

reduction

of slow

was responsible antral

by equivalent

contrac-

depolariza-

A - 30 mV - 70

contractions

membrane

muscle,

of

poten-

polarizations.

Figure 1. Effect of pregnancy on the force of phasic antral contrac-

of phasic

the reduced

a pregnant

by a plateau

potential

decreases

amplitude,

cir-

tractions from pregnant guinea pigs is associated with a reduction in the underlying electrical slow wave de-

10

Bethanechol Concentration (CtM)

force

and

slow wave frequency,

in the pregnant

an ex-

of antral

slow wave consists

smooth

15 virgin

but significant

plitude,

a virgin

that there

potentials,

duration

1

from

pigs show

2 shows

activity

to the resting

In guinea

occurred

Figure

followed

tial, and a repolarization

0.1

characterized

electrical

muscle

pig mid antrum with electrical

pig. The electrical

a fast upstroke

muscle

coupling,

or slow waves.

of intracellular smooth

of

associated

depolarizations cular

smooth

guinea

contractions

female

the mechanism

As seen in other species,‘4*16 in vitro

by spontaneous ample

Fehale

pigs to investigate

I

in virgin in absolute

force from bethanechol was significantly (P = 0.023) less in the pregnant animals than in the control virgin females. Thus, in addition to a decrease in the force of spontaneous phasic antral contractions, cholinergic-

- 69

stimulated contractions of antral smooth muscle were also decreased in the pregnant guinea pigs compared with the control virgin females.

Figure 2. Comparison of electrical slow waves of antral smooth mus-

Effect of Pregnancy Electrical Activity tained

Intracellular from antral

on Intracellular

electrical recordings were smooth muscle cells of virgin

oband

mV

’ 20 set

’

cle from (A) virgin and (B) pregnant guinea pigs. In the tracingfrom the virgin female (A), the electrical slow wave consists of a fast upstroke potential, followed by a plateau potential, then repolarization to the resting membrane potential. Fast spike wave activity is seen during the plateau potential. As seen in comparing these two examples, there are differences in the tracing from the pregnant female (B), i.e., a lower amplitude of the upstroke and plateau potential and an absence of fast spike wave activity during the plateau potential.

November

Table 1. Electrophysiological Characteristics of Antral Smooth Muscle Cells in Virgin and Pregnant Female Guinea Pigs Virgin (n = 15) Resting membrane potential (mV)

Pregnant (n = 20)

previously reported in the guinea piga3,24 and in other 1, of depolarization species, lb in which the amplitude during the slow wave, primarily the plateau potential, correlates P value

cellular

with the force of contraction.25’26 electrical

f

1.5

+ 1.2

-68.9

NS

5.9 f 0.2

6.3 f 0.3

NS

Upstroke amplitude (mV) Plateau amplitude (mV)

31.7 f 1.1 27.2 + 0.9

25.5 k 1.4 23.7 + 1.6

0.002 0.048

No. of spikes per slow wave Slow wave duration (s)

1.3 + 0.3 6.8 f 0.2

0.6 f 0.1 6.4 rt 0.3

0.017 NS

the

presence

of

as mean f SEM. P values were ob-

t test.

have smooth

been

(20

while

change

by using

mmol/L)

were

recorded

sium

concentration

in tone

and

progressive potential

was observed

change

in tonic

females

are shown

tested (-69 0.10)

pregnant This

equivalent

muscle

progressively

of the

spike wave

Increases

virgin

range (P >

relationship

guinea levels

when

the

and bethanechol-induced

antral

contractions

during

termine

is decreased

and

with alterations numerous

gastrointestinal

ion channels canine

antral

examined pregnant

trode

recording

cording

that pregnancy

muscle

techniques.

motil-

have attempted

by which

phasic

The fmd-

in gastrointestinal

gastrointestinal animals using

of mechanical

muscle

pregnancy.

studies

smooth

have from

circular

with the hypothesis

the mechanisms

to de-

pregnancy

affects

contractility,

none

tract smooth muscle intracellular microelecWe used simultaneous

and electrical

activity

re-

to test the

A

C-F

0.20 ;;‘

pigs were compared.

c .o E 5

an

is produced.

F .g P

that pregnancy

studies

have

shown

that

de-

layed gastric emptying occurs during pregnancy in the guinea pig. l3 Second, the reproductive physiology of the female guinea pig has features in common with humans, including elevated levels of serum progesterone and estrogen during pregnancy.22 Third, the regional gastric motility in guinea pigs is similar to that in humans.13 The electromechanical coupling of antral smooth muscle recorded in this study is similar to that

60set

B

of depolarization,

affects the electromechanical activity of antral smooth muscle. The guinea pig model was chosen for several previous

pig

and

poten-

This study shows that the force of both spontaneous

$

This study tested the hypothesis

First,

in guinea

and pregnant

Discussion

reasons.

plateau

and the

3B. In the voltage

tension

the

in both

mV), there was no difference

at equal

during

from

by potassium

between

voltage-tension that

the potas-

animals,27

of the slow waves

of phasic contractions ocThe effects of the change

in Figure

and the virgin

shows

potential

When

3A).

induced

tension

to -49

in the

membrane

of

muscle

depolarization

(Figure

potential

the

and increased

baseline tone and amplitude curred with depolarization. in membrane

concentration

depolarize

was increased

membrane

activity

to

simultaneously.‘4*21

4.6 to 20 mmol/L, resting

a high

that in other

muscle.28T29

is associated

was studied

pig antrum

types of cell membrane

ings are consistent

tions in pregnant and virgin guinea pigs were tested. This voltage-tension relationship of the antral smooth

than

spikes

shown

ity.’ Although

potassium

different

The intra-

of the guinea

as seen in the faster frequency tial. 16,23,24Similar

NOTE. Results are expressed tained by unpaired Student’s

the

activity

may be slightly -69.8

Slow wave frequency (per min)

muscle

1309

DECREASED ANTRAL CONTRACTILITY IN PREGNANCY

1993

1

0.15. I

O.lO-

a i 1 1

0.05.

0.00-l

T

I

1

1.

-69

-64 -59 -54 -49 Membrane Potential (mv)

Figure 3. Effect of increasing potassium concentration

on electromechanical activity of antral smooth muscle from a virgin female guinea pig. (A) Slowly changing the potassium concentration from 4.6 to 20 mmol/L (arrow) results in a progressive depolarization of the resting membrane potential and increased spike wave activity. With depolarization, there is an increase in baseline tone and amplitude of phasic contractions. (8) The voltage-tension relationship ofthree pregnant (0) and three virgin (0) female guinea pig antral muscle strips (each strip from a different animal). This graph depicts increasing membrane potential in response to potassium and the tonic tension produced. In the voltage range tested, there was no change in the voltage-tension relationship between pregnant and virgin guinea pigs.

1310

PARKMAN

hypothesis

ET AL.

GASTROENTEROLOGY

coupling

of antral

especially potassium,

smooth muscle is altered during pregnancy.

that electromechanical

In antral

likely that the resting membrane

muscle from pregnant animals, the decreased spontane-

responsible

lar in both groups of animals.

depolarization,

as manifested

by a decreased upstroke

on

per slow wave. Experiments

changes in the expression

sion with

increased

potassium

using perfu-

concentration

were

used to test whether the decreased contractility

in an-

voltage-dependent

calcium

may be a fundamental

mechanism

tral smooth muscle from pregnant guinea pigs was re-

ther elucidate

waves during pregnancy,

electrical

slow waves causing a decrease

mobilization

in calcium

or to a change in the ability of calcium to

directly activate muscle contraction.30 age-tension

of the

relationship

Because the volt-

in muscle from pregnant and

channel

resulted

wave depolarization bilization.

from

a diminished

causing a decrease in calcium mo-

This suggests that similar forces would be

generated if the electrical

slow waves were similar. A

similar decrease in electromechanical ished

slow

slow-wave

plateau

amplitude

activity (diminand decreased

the mechanism

of altered antral slow

measurement

The decreased electromechanical

administration

animals

in the regulation of

during pregnancy.33 To furof membrane in iso-

activity in guinea

pig antral smooth muscle is likely to be mediated by the hormonal

pregnant

Thus,

lated cells may be required.

reduced contractility

muscle from

effect

ion channels

activity using patch clamp techniques

control animals was similar, it was concluded that the of antral smooth

estrogens

channels.34,35

of membrane

smooth muscle excitability

lated to either the decrease

in the amplitude

potential are simi-

In addition,

may have a direct inhibitory

and plateau amplitude and a reduced number of spikes performed

potassium channels

for the transmembrane

and progesterones

No. 5

across the cell membrane,26 it is

ous force is associated with a diminished

slow wave

Vol. 105,

tractility

changes during pregnancy. Progesterone has been shown to decrease antral con-

in vitro. 36 Similar effects have been reported

in gallbladder,

lower esophageal

sphincter,

and co-

ionic smooth muscle.37-3” Although studies using exogenous progesterone determine

administration

the mechanism

the short-term

in vitro may help

of decreased contractility,

administration

of progesterone,

a cho-

force generation to agonists) has been reported in elec-

lesterol-like

tromechanical recordings of surgically removed antral tissue from a patient with delayed gastric emptying and

cell membrane4’ and produce nonspecific effects. An example of this has been reported in the guinea pig

tachygastria. 31 Prior

studies in our laboratory

shown that the decrease in contractility

have

of gastrointes-

compound,

gallbladder.

Both

progesterone

pregnancy

However,

an alteration in the affinity of muscarinic

appear to be different:

the mechanisms

the smooth muscle.32 We did not investigate the underlying cellular mech-

lular calcium

anism for the electrical

pregnancy,long-term

pregnancy.

slow wave disturbance

The upstroke

depolarization

wave brings the membrane which membrane

potential

during

of the slow

into a range in

calcium channels are activated. The

and administration

of

in vitro result in decreased contractility.

tinal smooth muscle during pregnancy is not caused by receptors on

may change the fluidity of the

of decreased

pregnancy

utilization,3,‘9

vitro may alter extracellular

contractility

may affect intracel-

whereas progesterone

in

calcium influx.37 During

elevations

of progesterone

may

result in changes in gene expression leading to an alteration of intracellular long-term

or membrane

administration

properties.4’ Thus,

of progesterone

in vivo may

resultant influx of calcium through these voltage-de-

be a better model to study the hormonal

pendent calcium channels leads to an increase in cyto-

pregnancy. Supporting the concept that the decreased electromechanical activity is mediated by progesterone

solic

calcium

concentration,

which

activates

the

contractile elements.25*26 During the slow wave depolarization, membrane potassium channels may open, allowing repolarization to the resting membrane potential.27 Alterations or differential expression of these ion channels may affect the electrical slow wave and antral contractility. Hormonal regulation of membrane potassium channels by estrogen during the estrous cycle and pregnancy has been shown in uterine smooth muscle cells. 33 Because the resting membrane potentials were similar in the pregnant and virgin guinea pigs and the resting membrane potential is a function of the gradients and permeabilities of ions,

changes of

are studies in male rats showing that antral contractility is reduced when rats are pretreated

in vivo with

progesterone. 42 Delayed gastric emptying has also been shown in premenopausal women and postmenopausal women on sex hormone replacement therapy.43 Although the present study suggests decreased antral contractility as a cause of delayed gastric emptying during pregnancy, other mechanisms may also play a role. Regulation of gastric emptying is an interplay between several factors other than antral contractility. Abnormalities in fundic tone, pyloric pressure, duodenal pressure, frequency of antral contractions, and

November

DECREASED

1993

antropyloroduodenal

coordination

may also be impor-

tant. Progesterone has been shown to decrease the propagation velocity of gastrointestinal slow waves possibly

by decreasing

between

smooth

the degree of electrical

muscle

such as tachygastria

or bradygastria,

lated to symptoms

of nausea,

ing the first trimester In conclusion, of spontaneous during the The

results

pregnancy chanical

cholinergic

antral

Herlihy muscle

19.

Ryan JP. Calcium and gallbladder smooth muscle contraction in the guinea pig: effects of pregnancy. Gastroenterology 1985;

1991;261:G78-G82.

electrical that

slow

wave

delayed

from

89:1279-1285. 20.

Daniel WW. Biostatistics: a foundation sciences. New York: Wiley, 1983.

force

21.

Morgan KG, Muir TC, Szurszewski JH. The electrical basis for contraction and relaxation in canine fundal smooth muscle. J Physiol (Lond) 1981;311:475-488.

22.

Batra S, Sjoberg N-O, Thorbert G. Sex steroids in plasma and reproductive tissues of the female guinea pig. Biol Reprod 1980;22:430-437.

23.

Ohba M, Sakamoto Y, Tomita T. The slow wave in the circular muscle of the guinea-pig stomach. J Physiol (Lond) 1975;

of the gastric

smooth

a change

in

depolarization.

gastric

alterations

emptying

in

in electromemuscle.

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Received August 10, 1992. Accepted July 20, 1993. Address requests for reprints to: Henry P. Parkman, M.D., Gastroenterology SeCtIOn, Department of Medlclne, Parkinson Pavilion, 8th Floor, Temple University Hospital, 3401 North Broad Street, Phlladelphia, Pennsylvania 19140. Portlons of this manuscript were presented at the 1992 American Gastroenterological Association meetlng and appeared In abstract form (Gastroenterology 1992;102:A499).